Biosynthesis of glutathione during glutathione depletion appears to be of critical importance for certain vital organs during overexposure to a variety of chemical agents including acetaminophen, styrene oxide and certain halogenated substances, e.g., 1,2-dibromoethane, 1,2-dichloroethane and 1,1 dichloroethylene. It is proposed to examine the role of the cystathionine pathway in these organs in the replenishment of both the intracellular cysteine and glutathiione content of the liver, kidney, lung and testes. Regulation of this pathway as well as the conversion of cysteine to sulfate will be a part of the overall study of regulation of cysteine and glutathione in these tissues. An antidotal protocol for minimizing organ damage during exposure to glutathione depleting agents, especially certain halogenated solvents, will be developed with small animals for application in clinical treatment of humans. It is anticipated that methionine and/or N-acetylcysteine will serve very well in such a protocol.